The International Working Group on Morphology of MDS (IWGM-MDS)
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1 The International Working Group on Morphology of MDS (IWGM-MDS) Barbara J. Bain, St Mary s Hospital Imperial College, London, UK John M. Bennett, University of Rochester, NY, USA Richard Brunning, University of Minnesota, USA Jean E. Goasguen, University of Rennes, France Masao Tomonaga, University of Nagasaki, Japan Maria-Teresa Vallespi, Vall d Hebron Hospital, Barcelona, Spain Gina Zini, Haematology Institute, Catholic University of Sacred Heart, Rome, Italy Statistician: Alain Renault, University of Rennes and INSERM-CIC P 0203, France
2 WHO 2 RCUD R cytopenia with unilineage dysplasia * (Anemia, neutropenia, thrombopenia) Uni or bicytopenia BM: < 5% blasts RARS R cytopenia with Ring sideroblasts BM: >15% ring BM: <5% blasts RCMD R cytopenia with mulgple dysplasia Dysplasia in more >10% of the cells in 2 or 3 lineages RAEB- I RA with excess of blasts** Blood: <5% blasts BM: 5 to 9% blasts RAEB- II RA with excess of blasts Blood: 5 to 19% blasts BM: 10 to 19% blasts MDS- U unclassified Blood: cytopenias <1% blasts BM: Dysplasia in <10 cells of one or more lineage. CytogeneGc. <5% blasts MDS 5q- Anemia, Platelet, MGK 5q- * bi- cytopenia may be observed ** if 2-4% blasts in blood and <5% in BM: RAEB- I
3 nemia eutropenia hrombopenia
4 Quels sont les difficultés ou les pièges? L idengficagon des blastes L idengficagon des dysplasies QualitaGvement: DysE DysG DysM QuanGtaGvement: 10%??? Les «Ring» sidéroblastes: QualitaGvement QuanGtaGvement Les monocytes promonocytes
5 Sidéroblastes Type I = 1 à 5 grains Type II = 5 à 15 grains Type III= >15 grains en couronne >15% ring = ARS MDS/J.E.Goasguen 5
6 New proposal for Ring sideroblasts: Haematologica Nov;93(11): Definitions in the litterature: - Iron granules in perinuclear distribution, entire nucleus - Iron granules in perinuclear distribution, 1/3 nucleus - >5 granules - >10 granules New proposal: At least 5 granules in perinuclear distribution, surrounding the entire nucleus, or portion or 1/3. 3 types of sideroblasts: <5 granules >= 5 granules not perinuclear >= 5 granules perinuclear
7 Perinuclear Siderotic Granules New proposal: At least 5 granules in perinuclear distribution, surrounding the entire nucleus, or portion or 1/3.
8 Figure 4: Composite of iron stained erythroid precursors Absence of iron granules Single iron granules (type 1) Classical Ring sideroblast (type 3) Focal iron granules (type 2) Qualifies as Ring > 10 granules Scattered iron granules (type 3) (qualifies as ring - >10 granules)
9 Subtype Example Description Remarks Agranular blast Granular blast Promyelocyte Agranular blast with basophilic cytoplasm fine chromatin and nuleoli A subtype but with azurophilic granulations and absence of Golgi zone Azurophilic granulations and A clear visible Golgi zone characteristic in promyelocytes Type I blast in the FAB classification Includes Type II blast in FAB classification and Type III blast as defined by Goasguen et al Haematologica Nov;93(11): Myelodysplastic promyelocyte Promyelocyte with an irregular distribution of granulations and reduced number of granules Jean Goasguen These cells are often seen in MDS and need to be distinguished from granular blasts
10 A A G G G G G PMC PMC AbnPMC AbnPMC AbnPMC AbnPMC Jean Goasguen
11 N1 Golgi zone 1. Agranular Blast 2. Granular Blast 3. Promyelocyte 4. Abnormal Promyelocyte Jean Goasguen
12 P4 1. Agranular Blast 2. Granular Blast 3. Promyelocyte 4. Abnormal Promyelocyte Jean Goasguen
13 P16 1. Agranular Blast 2. Granular Blast 3. Promyelocyte 4. Abnormal Promyelocyte Jean Goasguen
14 Haematologica Jul;94(7):994-7.
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20 Dysplasie de la lignée granuleuse Qualité du fro1s, qualité de la colora7on 1. QuanGté de grains dans le cytoplasme: 2. Présence de grains anormaux 3. ChromaGne assemblée en mojes: le «Clumping» 4. SegmentaGon du noyaux: «Pelger Huet» 5. ProjecGons nucléaires ou appendices (caryoschizes) Leuk Res Apr;38(4):
21 R142 Male 83-year-old with: WBC: 1.5 x 10 9 /l Hb: 5.6 g/dl Plt 157 x 10 9 /l Neutrophils: 600 x 10 9 /l Lymphs: 650 x 10 9 /l Monos: 250 x 10 9 /l Bone Marrow: 8% blasts with DysG DysE DysM A1 A A3 A4 A5 A6 1 A7 A8 A9 A10
22 Results R142: 0% granules 100% granules # # # # # # /3
23 R142: Means of ranks with standard deviation for granularity: Mean ranks ,2 2,2 2,7 4,8 5,2 5,7 6,7 8,3 8,8 9,5 devt 0,4 0,8 0,5 1,6 1,0 0,8 0,8 1,5 0,8 0,8 A10 A6 A5 A3 A7 A2 A9 A8 A1 A4 2/3 reducgon granules
24 3rd part: Dysgranulopoiesis: Macropolycytes Macropolycytes: Neutrophils with large size May have double nuclear mass Dysmorphic nucleus Inclusion with dysmorphic neutrophils
25 Normal size
26 15 consecutive neutrophils from a child with an RAEB/AML2 In which you have to identify: Pelger, and Clumping, P8 P4 P3 P2 P1 P9 P7 P5 P6 P10 P15 P13 P11 P12 P14
27
28 4th part: Nuclear ProjecGons DefiniGon: Kosonow and Scupin: (1956) Acta Haematologica 1956, 15, 349. P9 P9 from R#15 Appendage type C
29 Kosonow and Scupin: (1956) Acta Haematologica 1956, 15, 349. Nuclear projecgons have been described using different terms such as: Nuclear projecgons or Sex appendages DrumsGck Nuclear pockets Vesicular appendages Nuclear vesicles The paper from Kosonow classify these chromagn extension in 4 categories: Type A: (sex related) Type B: Type C: Type D:
30 Nuclear ProjecGons Cells with more than 4 NP were not observed in healthy people, and there is a trend To have more NP in the MDS population (see Somers test).
31 Conclusions: Neutrophils: Granularity: 2/3 loss Pelger: 95% concordance Abnormal segmentagon: 91% ChromaGn Clumping: 71% AssociaGon Pelger and Clumping: p=0,002 Macropolycytes: include as dysplas7c Nuclear projecgons: >4NP Eosinophils and Basophils Eosinophils Basophils
32 DysM Micromega Méga mononucléaire MDS/J.E.Goasguen 32
33 DysM Petits noyaux ronds multiples et séparés Plaquettes matures MDS/J.E.Goasguen 33
34 DysM Petits noyaux ronds multiples et séparés cytoplasme granuleux MDS/J.E.Goasguen 34
35 DysM Megacaryoblaste CD41 MDS/J.E.Goasguen 35
36 DysM 5q- MDS/J.E.Goasguen 36
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